The sources on B12 and fatigue, mood or wellbeing do not point the same way, and several report no difference from placebo. A systematic review and meta-analysis states that in most cases such complaints are not associated with overt vitamin B12 deficiency, and that the effectiveness of vitamin B12 supplementation in such cases is uncertain. This guide sets out what each source measured, in whom and in what form.
What the reviews say
The same review says vitamin B12 is often used to improve cognitive function, depressive symptoms and fatigue. A systematic review and meta-analysis of randomized controlled trials found no overall effect of vitamin supplementation on measures of depression. It also reported that only one study reported effects on idiopathic fatigue, and therefore no analysis was possible.
What each trial measured
Each row names the people studied and the form used, because a result in one group does not carry over to another. Where a cell says "not given here", this guide has no figure for it.
| Trial | People studied | Form, dose and length | What the source reports |
|---|---|---|---|
| Randomized, placebo-controlled trial | 95 out-clinic patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), deactivating fatigue and normal vitamin B12 blood levels (≥150 pmol/l), aged 18-65 years. Normal levels, so not a deficiency group. | 1000 μg vitamin B12 daily or a placebo supplement for 8 weeks. Form not given here. | The authors concluded that the study did not confirm the expected effect of non-conventional surplus vit B12 supplementation on fatigue. |
| Randomized, placebo-controlled study | Participants with biochemical signs of vitamin B-12 deficiency. | Vitamin B-12 injection or placebo weekly for 4 weeks, re-examined 3 months later. The abstract does not state the injection dose. | Vitamin B-12 treatment influenced only one of eight dimensions of health-related quality of life (HRQOL). |
| Double-blind, placebo-controlled crossover trial | 15 patients who met the Centers for Disease Control criteria for chronic fatigue syndrome. B12 status not given here. | Intramuscular LEFAC, an injectable bovine liver extract containing folic acid and cyanocobalamin. This is a combined product, not cyanocobalamin alone. The abstract does not state a dose. Length not given here. | Patients responded to placebo and LEFAC by several criteria of functional status. No significant difference was apparent between response to placebo and that to LEFAC. |
| Randomized controlled trial | Patients with depression and low normal B12 levels, so not a deficiency group. | Antidepressant only (control) or antidepressants plus injectable vitamin B12 supplementation. The abstract does not state the dose or mention a placebo. Follow up at three months; treatment length not given here. | At three months follow up 100% of the treatment group showed at least a 20% reduction in HAM-D score, while only 69% in the control arm did (p<0.001). |
| Randomized double-blind trial | Healthy humans, as the source title describes them. | Vitamin B complex, a multi-vitamin B product and not a single vitamin. Dose and length not given here. | A significant increase in the running time by 1.26-fold (p < 0.05) to exhaustion compared to that before supplementation and that in the placebo group. |
How to read these results
The IBS and IBD trial and the depression trial concern people with normal or low normal levels, and the running trial concerns healthy humans. The injection study concerns people with biochemical signs of deficiency. The liver extract trial does not give B12 status.
The depression trial reports a difference on a rating scale, but its control arm received antidepressant only and no placebo is mentioned, so it is not a placebo comparison. The liver extract trial tested a combined product, so its result cannot be assigned to cyanocobalamin alone. The running trial did not test a single vitamin.
How injections were used in 1985
An observational analysis in Family Medicine (the NAMCS analysis) indicates that of the calculated 2,516,564 vitamin B12 injections given in 1985, only 376,488 were for a diagnosis compatible with a cobalamin deficiency state (a 7:1 observed over expected ratio). The figures count injections by diagnosis. They say nothing about whether any injection changed how someone felt. Observational data cannot show cause and effect.
What this does not tell you
These sources cannot tell you what a B12 injection would do for your own energy, mood or wellbeing. The trials differ in people, form, dose and length, and some abstracts do not state the dose. A result in people with normal or low normal levels is not a result for people with a deficiency, and the reverse is also true. Whether a symptom has anything to do with B12 status is a question for a licensed provider.